Obesity, and especially upper body obesity, is the most common nutritional disorder in the over-nourished populations of the world. Current methods for promoting weight loss are not completely satisfactory. Unfortunately, an estimated 33 billion dollars a year are spent on weight-loss measures that are largely futile. Thus, new methods and compositions such as pharmaceutical agents that promote weight-loss are urgently needed to complement old approaches.
Fibroblast growth factor 21 (FGF-21) belongs to a family of large polypeptides widely expressed in developing and adult tissues that play crucial roles in multiple physiological functions. FGF-21 has been reported to stimulate glucose-uptake in mouse adipocytes after prolonged treatment, in the presence and absence of insulin, and to decrease fed and fasting blood glucose, triglycerides, and glucagon levels in ob/ob and db/db mice in a dose-dependent manner, thus, providing the basis for the use of FGF-21 as a therapy for treating diabetes and obesity (WO03/011213).
In addition to its beneficial effects on Type 2 diabetes, Glucagon-like peptide-1 (GLP-1) compounds have been described for the treatment of obesity, (WO98/019698). Although both FGF-21 and GLP-1 compounds have shown positive effects in treating obesity, there has not been any indication that a combination of FGF-21 compounds and GLP-1 compounds would provide a synergistic effect on lowering body weight. There is thus, still a need for additional beneficial therapeutics for weight loss.
Applicants have determined that a combination of an FGF-21 compound and a GLP-1 compound have an unexpected synergistic effect on lowering body weight.